Causes of Hypoparathyroidism
Hypoparathyroidism results from inadequate parathyroid hormone (PTH) secretion or action, with postsurgical injury being the most common cause (75% of cases), followed by genetic disorders, autoimmune conditions, and infiltrative diseases. 1
Surgical Causes (Most Common)
Inadvertent removal of or injury to the parathyroid glands during neck surgery accounts for three-quarters of all hypoparathyroidism cases. 2, 1 This includes:
- Thyroidectomy (most frequent surgical cause) 3
- Parathyroidectomy 3
- Radical neck dissection for cancer 3
- Other neck surgeries involving manipulation near parathyroid tissue 2
A critical pitfall: transient postsurgical hypoparathyroidism must be distinguished from permanent forms, as temporary dysfunction can persist for months before recovery, potentially leading to unnecessary lifelong replacement therapy. 3
Genetic Causes
22q11.2 deletion syndrome carries an 80% lifetime prevalence of hypoparathyroidism due to underlying parathyroid dysfunction, making it the most important genetic cause to recognize. 4, 5 Key features include:
- Hypocalcemia can emerge or recur at any age, even after apparent childhood resolution 4
- The majority of patients with neonatal hypocalcemia will experience recurrence later in life 4, 6
- Approximately 60% of children with this syndrome develop hypocalcemia 4
Other genetic causes include isolated hypoparathyroidism and syndromic forms that require systematic genetic evaluation. 7, 3
Autoimmune Causes
Autoimmune hypoparathyroidism remains a diagnosis of exclusion, as no specific autoantibodies are currently available for definitive diagnosis. 3 This can occur as:
Infiltrative and Metastatic Causes
- Metastatic disease to the parathyroid glands 1
- Infiltrative disorders (hemochromatosis, Wilson disease, granulomatous disease) 1
- Mineral deposition in parathyroid tissue 1
Radiation-Induced
Radiation therapy to the neck can cause delayed parathyroid gland failure. 1
Magnesium-Related (Critical to Recognize)
Magnesium deficiency impairs PTH secretion and creates PTH resistance—hypocalcemia will not resolve until magnesium levels are corrected first. 5, 6 Conversely, severe hypermagnesemia can also suppress PTH secretion. 1
This is a common diagnostic pitfall: always check magnesium levels in all hypocalcemic patients, as calcium supplementation will be ineffective without adequate magnesium. 5, 6
Idiopathic
When no cause can be identified after thorough evaluation, the diagnosis is idiopathic hypoparathyroidism, though this should only be assigned after excluding all other etiologies. 1, 3
High-Risk Precipitating Factors
Even in patients with underlying parathyroid dysfunction who appear stable, hypocalcemia can be triggered by biological stressors:
- Surgery, fractures, injuries 4, 5, 6
- Childbirth and pregnancy 4, 6
- Infection and acute illness 4, 6
- Fever, ischemia, hypoxia 4, 6
- Puberty 4, 6
- Decreased oral calcium intake 6
Targeted calcium monitoring should be performed during these vulnerable periods, particularly perioperatively and perinatally. 4
Exacerbating Factors
- Alcohol consumption worsens hypocalcemia 4, 5, 6
- Carbonated beverages, especially colas, may exacerbate hypocalcemia 4, 5, 6
- Certain medications (antipsychotics, loop diuretics) can precipitate or worsen hypocalcemia 4, 6
Diagnostic Approach
Always measure pH-corrected ionized calcium rather than total calcium alone, as a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L. 5, 6
The essential laboratory evaluation includes:
- pH-corrected ionized calcium (most accurate) 5, 6
- PTH level to distinguish PTH-mediated (low/normal PTH) from non-PTH-mediated causes (elevated PTH) 5
- Magnesium level (must be corrected before calcium) 5, 6
- Vitamin D status (25-OH vitamin D) 5
- Phosphate level 2
- Creatinine to assess renal function 4
For non-surgical cases, pursue systematic clinical and genetic evaluation to define the precise diagnosis, as syndromic forms require screening for associated abnormalities. 3